Key result
Eplerenone reduced heart failure hospitalization or cardiovascular death more in HFrEF patients with insulin-treated diabetes (HR 0.31; 95% CI 0.19-0.50) than in those without (interaction P=0.007).
Why the study?
Patients with HFrEF and insulin-treated diabetes have a high risk of cardiovascular complications, and whether mineralocorticoid receptor antagonists such as eplerenone mitigate this risk was explored.
Does eplerenone reduce the composite of heart failure hospitalization or cardiovascular death in patients with HFrEF, particularly those with insulin-treated diabetes?
RCT (n=2,737)
Does eplerenone reduce the composite of heart failure hospitalization or cardiovascular death in patients with HFrEF, particularly those with insulin-treated diabetes?
Eplerenone provides a profoundly magnified clinical benefit in HFrEF patients with insulin-treated diabetes, with an annualized number needed to treat of just 3 to prevent cardiovascular death or heart failure hospitalization.
May support preferential eplerenone benefit in insulin-treated diabetes with HFrEF; hypothesis-generating and requires prospective confirmation before practice change.
Background: Patients with heart failure with reduced ejection fraction (HFrEF) and insulin-treated diabetes have a high risk of cardiovascular complications. Mineralocorticoid receptor antagonists may mitigate this risk. We aim to explore the effect of eplerenone on cardiovascular outcomes and all-cause mortality in HFrEF patients with diabetes, including those treated with insulin in the EMPHASIS-HF trial (Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms). Methods: The primary outcome was the composite of heart failure hospitalization or cardiovascular death. Cox models with treatment-by-diabetes subgroup interaction terms were used. Results: The median follow-up was 21 (10–33) months. Of the 2737 patients included, 623 (23%) had non-insulin-treated diabetes, 236 (9%) had insulin-treated diabetes and 1878 did not have diabetes. Patients with insulin-treated diabetes were younger, more often women, with higher body mass index, waist circumference, more frequent ischemic heart failure cause, impaired kidney function, and longer diabetes duration. Compared with patients without diabetes, those with insulin-treated diabetes had a 2-fold higher risk of having a primary outcome event. The hazard ratio (95% CI) for the effect of eplerenone, compared with placebo, on the primary outcome was 0.31 (0.19–0.50) in insulin-treated diabetes, 0.69 (0.50–0.93) in non-insulin-treated diabetes, and 0.72 (0.58–0.88) in patients without diabetes; interaction P =0.007. The annualized number needed-to-treat-to-benefit with regards to the primary outcome was 3 (95% CI, 3–4) in patients with insulin-treated diabetes, 16 (13–19) in patients with diabetes not receiving insulin, and 26 (24–28) in patients without diabetes. Conclusions: Patients with insulin-treated diabetes experienced a greater benefit from eplerenone than those with diabetes not treated with insulin and people without diabetes. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00232180.
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Ferreira et al. (2021) conducted an RCT in Heart failure with reduced ejection fraction (HFrEF) (n=2,737). Eplerenone vs. Placebo was evaluated on Composite of heart failure hospitalization or cardiovascular death (HR 0.31, 95% CI 0.19-0.50, p=0.007). Eplerenone reduced heart failure hospitalization or cardiovascular death more in HFrEF patients with insulin-treated diabetes (HR 0.31; 95% CI 0.19-0.50) than in those without (interaction P=0.007).
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